The purpose of this study was to clarify the distribution of epidermal growth factor receptor (EGFR) mutations between primary tumors (PT) and metastatic lymph node (MLN) in patients with resected non-small cell lung cancer (NSCLC) and to identify a better predictive marker of the response to EGFR tyrosine kinase inhibitor (EGFR-TKI). We conducted a retrospective review of the data of 70 lung cancer patients with lymph node metastasis who underwent surgical resection. Analysis to detect EGFR mutations was performed by a peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. EGFR mutations were detected in 15.7 % of both the PT and MLN and in 14.3 % of the PT only. The response rate to EGFR-TKI tended to be higher in patients with EGFR mutations in the MLN, as all patients with EGFR mutations in the MLN showed disease control to treatment with EGFR-TKI. Our results demonstrated that the EGFR mutation status of MLN is a predictive marker of the response to EGFR-TKI therapy in patients with recurrent NSCLC after surgical resection.